μ阿片受体激动剂PL017对内脏痛和胃肠功能的调节作用

Effects ofμopioid receptor agonist PL017 on visceral pain and gastrointestinal function

目的探究μ阿片受体激动剂[MePhe3,D-Pro4]morphiceptin (PL017)在外周水平对小鼠内脏痛和末端结肠的调节。方法用醋酸扭体模型评价药物对外周内脏痛的调节。排珠实验评价末端结肠的运动能力。排便实验综合反映药物对大肠、小肠和胃的调节效果。结果(1)皮下注射PL017在扭体模型中表现出显著的剂量依赖性的强效镇痛(ED50=9.76±1.36μg·kg^(-1));(2)拮抗剂组结果表明,PL017的外周镇痛由μ阿片受体介导;(3)抑制排珠和排便的有效剂量远高于其外周镇痛剂量。结论探究了PL017在醋酸扭体模型中的外周镇痛活性;相较于胃肠调节,PL017对内脏痛的镇痛活性更高,提示PL017可能具有一定治疗外周内脏痛的潜力。

Objective The present study aimed to investigate the effects of μ opioid receptor agonist [MePhe3,D-Pro4] morphiceptin （PL017） on visceral pain and colonic bead expulsion in mice. Methods Writhing model induced by subcutaneously injection of acetic acid was utilized to evaluate the peripheral visceral pain.Bead expulsion was measured to evaluate the colonic motility.Fecal pellet output was considered to reflect a combination of the actions on stomach,small and large intestine. Results （1） Subcutaneous PL017 demonstrated the potent and dose-dependent analgesia in writhing test （ED 50 =9.76±1.36 μg·kg -1 ）;（2）mechanism results indicated that PL017-induced visceral analgesic effects might be mediated via μ opioid receptor;（3）subcutaneous PL017 delayed bead expulsion latency and fecal pellet output with the dose far higher than its visceral analgesic dose. Conclusion The potent analgesic bioactivity of PL017 was explored by acid-induced writhing test;PL017 possessed a high bioactivity of visceral pain relief without causing gastrointestinal disorder,suggesting its therapeutic potential to relieve visceral pain.